AIMS

To examine the association of fasting insulin, insulin resistance and reduced β-cell function with incident Type 2 diabetes and pre-diabetes (isolated impaired fasting glucose/isolated impaired glucose tolerance and combined impaired fasting glucose/impaired glucose tolerance).

METHODS

An Iranian population comprising 1532 men and 2221 women, aged ≥ 20 years, with normal fasting glucose and normal glucose tolerance at baseline, were enrolled in the study. Multivariable Cox proportional hazard models were used to calculate the hazard ratios and 95% CIs of fasting insulin, updated homeostasis model assessments of insulin resistance and β-cell function for incident Type 2 diabetes, isolated impaired fasting glucose, isolated impaired glucose tolerance and combined impaired fasting glucose/impaired glucose tolerance.

RESULTS

During a median follow-up of 9.2 years, the annual incidence rates (95% CI) of diabetes were 3.73 (2.74-4.94) and 4.06 (3.21-5.06) per 1000 person-years in men and women, respectively. In both men and women, fasting insulin and homeostasis model assessment of insulin resistance (≥ 75th percentile) were significantly associated with incident diabetes and combined impaired fasting glucose/impaired glucose tolerance; however, reduced β-cell function as measured by homeostasis model assessment of β-cell function (< 25th percentile) was associated with incident isolated impaired fasting glucose solely in men [hazard ratio 1.35 (95% CI 1.02-1.78)] in multivariable analysis including waist-hip ratio). Hyperinsulinaemia, insulin resistance and β-cell dysfunction were not related to the incidence of isolated impaired glucose tolerance in either gender.

CONCLUSIONS

Fasting hyperinsulinaemia and insulin resistance were strong risk factors for progression to diabetes and combined impaired fasting glucose/impaired glucose tolerance in a population with normal fasting glucose/normal glucose tolerance. In addition, impaired β-cell function at baseline was related to the development of isolated impaired fasting glucose only in men and, in both men and women, neither insulin resistance nor β-cell dysfunction were associated with incident isolated impaired glucose tolerance.